TY - JOUR
T1 - SKA3 Promotes tumor growth by regulating CDK2/P53 phosphorylation in hepatocellular carcinoma
AU - Hou, Yuchen
AU - Wang, Ziming
AU - Huang, Shanzhou
AU - Sun, Chengjun
AU - Zhao, Jingya
AU - Shi, Jiayu
AU - Li, Zhongqiu
AU - Wang, Zekang
AU - He, Xiaoshun
AU - Tam, Nga Lei
AU - Wu, Linwei
N1 - Funding Information:
We would like to show our deepest gratitude to FangXing Li for his careful work and thoughtful suggestions that have helped improve this paper substantially. This work was supported by the National Natural Science Foundation of China (grant 81670592); the Natural Science Foundation of Guangdong Province, China (grant 2016A030313242); the Science and Technology Program of Guangzhou, China (grant 201804020075); the Fundamental Research Funds for the Central Universities (grant 17ykjc09); and the Ke Lin Programme Foundation for Youth Talents (grant y50181); Guangdong Provincial Key Laboratory Construction Projection on Organ Donation and Transplant Immunology (No.2013A061401007); and Guangdong Provincial international Cooperation Base of Science and Technology (Organ Transplantation) (No.2015B050501002).
Publisher Copyright:
© 2019, The Author(s).
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Spindle and kinetochore-related complex subunit 3 (SKA3) is a component of the spindle and kinetochore-related complexes and is essential for accurate timing of late mitosis. However, the relationship between SKA3 and hepatocellular carcinoma (HCC) has not yet been fully elucidated. Gene expression omnibus (GEO) (GSE62232, GSE45436, GSE6764, and GSE36376) and The Cancer Atlas (TCGA) datasets were analyzed to identify differential expression genes. Cell proliferation ability was analyzed using Cell Counting Kit-8 (CCK8) assay and plate clone formation assay, while scratch wound healing assay and transwell assay were used to analyze cell invasion. The role of SKA3 in vivo was explored using subcutaneous xenotransplantation model and lung metastasis model. Bioinformatics analysis found that hepatocellular carcinoma patients with high levels of expression of SKA3 have a poor prognosis. Similarly, immunohistochemical staining of 236 samples of tumors also found higher SKA3 expression in them, than in adjacent normal liver tissues. Significant levels of inhibition of in vivo and in vitro tumor proliferation and invasion result from the downregulation of SKA3. Mechanistically, SKA3 was found to affect tumor progression through the cell cycle and P53 signaling pathway as shown by the gene enrichment analysis (GSEA). G2/M phase arrest and severe apoptosis was also found to result from SKA3 knockdown, as shown by the inhibition of CDK2/p53 phosphorylation together with downregulation of BAX/Bcl-2 expression in HCC cells. Overall, these findings uncover the role of SKA3 in regulating the apoptosis and proliferation of hepatocellular carcinoma cells. This study was able to uncover new information on the tumorigenesis mechanism in hepatocellular carcinoma.
AB - Spindle and kinetochore-related complex subunit 3 (SKA3) is a component of the spindle and kinetochore-related complexes and is essential for accurate timing of late mitosis. However, the relationship between SKA3 and hepatocellular carcinoma (HCC) has not yet been fully elucidated. Gene expression omnibus (GEO) (GSE62232, GSE45436, GSE6764, and GSE36376) and The Cancer Atlas (TCGA) datasets were analyzed to identify differential expression genes. Cell proliferation ability was analyzed using Cell Counting Kit-8 (CCK8) assay and plate clone formation assay, while scratch wound healing assay and transwell assay were used to analyze cell invasion. The role of SKA3 in vivo was explored using subcutaneous xenotransplantation model and lung metastasis model. Bioinformatics analysis found that hepatocellular carcinoma patients with high levels of expression of SKA3 have a poor prognosis. Similarly, immunohistochemical staining of 236 samples of tumors also found higher SKA3 expression in them, than in adjacent normal liver tissues. Significant levels of inhibition of in vivo and in vitro tumor proliferation and invasion result from the downregulation of SKA3. Mechanistically, SKA3 was found to affect tumor progression through the cell cycle and P53 signaling pathway as shown by the gene enrichment analysis (GSEA). G2/M phase arrest and severe apoptosis was also found to result from SKA3 knockdown, as shown by the inhibition of CDK2/p53 phosphorylation together with downregulation of BAX/Bcl-2 expression in HCC cells. Overall, these findings uncover the role of SKA3 in regulating the apoptosis and proliferation of hepatocellular carcinoma cells. This study was able to uncover new information on the tumorigenesis mechanism in hepatocellular carcinoma.
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U2 - 10.1038/s41419-019-2163-3
DO - 10.1038/s41419-019-2163-3
M3 - Article
C2 - 31804459
AN - SCOPUS:85076042891
VL - 10
JO - Cell Death and Disease
JF - Cell Death and Disease
SN - 2041-4889
IS - 12
M1 - 929
ER -